A great deal of evidence suggests an etiologic role for the sympathetic nervous system in human essential hypertension. The vascular mechanism through which the sympathetic nervous system may cause sustained hypertension is unknown. Recent studies from this laboratory have shown that selective renal sympathetic stimulation may be important in the production and maintenance of elevated blood pressure. The objective of the present research project is to further investigate the selective effect of the sympathetic nervous system on the kidney. A dog model of chronic central neurogenic hypertension is being developed by placing bilateral electrical lesions in the nucleus of the tractus solitarius. This model will be studied with respect to the hormonal, hemodynamic, and renal mechanisms involved in the pathogenesis of the hypertensive process. If this model is characterized by increased peripheral sympathetic nervous system activity as predicted, studies of the effects of renal denervation in preventing and reversing the hypertension will be performed. Studies will be performed to determine the mechanism for sustained hypertension in the conscious dog model of chronic intrarenal norepinephrine infusion. The reversability of hypertension after cessation of chronic norepinephrine administration will be observed. These studies should bring about a better understanding of the pathophysiology of human essential hypertension.